Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
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Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation. / Mailand, Niels; Lukas, Claudia; Kaiser, Brett K; Jackson, Peter K; Bartek, Jiri; Lukas, Jiri.
In: Nature Cell Biology, Vol. 4, No. 4, 04.2002, p. 317-22.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
AU - Mailand, Niels
AU - Lukas, Claudia
AU - Kaiser, Brett K
AU - Jackson, Peter K
AU - Bartek, Jiri
AU - Lukas, Jiri
PY - 2002/4
Y1 - 2002/4
N2 - We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.
AB - We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.
KW - Cell Cycle Proteins
KW - Cell Division
KW - Cell Line
KW - Cell Nucleus
KW - Centrosome
KW - Chromosomes
KW - Down-Regulation
KW - Flow Cytometry
KW - HeLa Cells
KW - Humans
KW - Immunoblotting
KW - Kinetics
KW - Microscopy, Fluorescence
KW - Microtubules
KW - Mitosis
KW - Mutation
KW - Phosphoric Monoester Hydrolases
KW - Plasmids
KW - Protein Tyrosine Phosphatases
KW - RNA
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
KW - Schizosaccharomyces
KW - Time Factors
KW - Transgenes
U2 - 10.1038/ncb777
DO - 10.1038/ncb777
M3 - Journal article
C2 - 11901424
VL - 4
SP - 317
EP - 322
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 4
ER -
ID: 124904249